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A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT05252364
Recruitment Status : Recruiting
First Posted : February 23, 2022
Last Update Posted : February 27, 2023
Sponsor:
Information provided by (Responsible Party):
Hinova Pharmaceuticals Inc. ( Hinova Pharmaceuticals Aus Pty Ltd )

Study Description
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Brief Summary:
The overall objective of this Phase 1 study is to evaluate the safety, PK, and anti-tumor activity of 12 weeks of daily oral dosing with HP518 after selecting the RP2D of HP518 based on assessments of multiple dose escalation in patients with progressive mCRPC.

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: HP518 - Dose Escalation Drug: HP518 - Dose expansion Phase 1

Detailed Description:
This First in Human dose escalation and expansion study of HP518 in patients with mCRPC is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide necessary information for efficacy analysis in future studies.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer
Actual Study Start Date : December 14, 2021
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : April 29, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 - Dose Escalation, 25mg/d (Cohort 1)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation, 50mg/d (Cohort 2)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 100mg/d (Cohort 3)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 200mg/d (Cohort 4)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 300mg/d (Cohort 5)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 400mg/d (Cohort 6)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 500mg/d (Cohort 7)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 600mg/d (Cohort 8)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 700mg/d (Cohort 9)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 1 - Dose Escalation 800mg/d (Cohort 10)
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose Escalation

Part 1: Dose escalation

Daily oral dosage with the prescribed dose level based on Cohort assignment.
Experimental: Part 2 - Dose Expansion
Oral tablet(s), once daily in 28-day cycles
 Drug: HP518 - Dose expansion

Part 2: Dose expansion

Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.


Outcome Measures
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Primary Outcome Measures :
  1. Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug [ Time Frame: 28 days ]
    To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

  2. Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

  3. Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

  4. Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [ Time Frame: Time Frame: Through study completion, an average of 1 year ]
    To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

  5. Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

  6. Proportion of patients showing a PSA decline of ≥50% between baseline and Week 12 of dosing with HP518. [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC) [ Time Frame: 12 weeks ]
  2. Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax) [ Time Frame: 12 weeks ]
  3. Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax) [ Time Frame: 12 weeks ]
  4. Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2) [ Time Frame: 12 weeks ]
  5. Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) [ Time Frame: 12 weeks ]
  6. Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F) [ Time Frame: 12 weeks ]
  7. Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518 [ Time Frame: 8 weeks ]
    To evaluate PSA50 from baseline to after 4 and 8 weeks of dosing with HP518

  8. Time to PSA progression using the PCWG3 definition (PSA >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart) [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate the time to PSA progression

  9. Time to radiographic progression using the RECIST v1.1 and PCWG3 definition [ Time Frame: Through study completion, an average of 1 year ]
    To evaluate radiographic progression per RECIST v1.1 and PCWG3

  10. Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline [ Time Frame: Through study completion, an average of 1 year ]
    To assess objective response by RECIST v1.1 (proportion of patients with a PR or CR) in patients with measurable soft tissue disease at baseline

  11. Change in number of AR N-term-positive CTCs/ml from baseline to week 12 [ Time Frame: 12 weeks ]
  12. Genomic profiling using cfDNA [ Time Frame: 12 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has histologically confirmed adenocarcinoma of the prostate.
  2. Has metastatic disease at study entry documented by 2 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.
  3. Has disease progression while receiving any ADT, androgen biosynthesis inhibitors, or second-generation AR inhibitors.
  4. Must have recovered from toxicities related to any prior treatments
  5. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
  6. ECOG performance status score of 0 to 1.

Exclusion Criteria:

  1. Has received more than 1 line of chemotherapy for prostate cancer.

  2. Use of enzalutamide, and/or other second-generation AR inhibitors and/or abiraterone as follows:

    • Received any agent within 4 weeks prior to the start of study drug.
    • Discontinued agent without evidence of radiographic or PSA progression.
  3. Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177Lu-PSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.
  4. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
  5. Has significant cardiovascular disease.

  6. Use of an investigational agent, without evidence of radiographic or PSA progression, within 4 weeks prior to the first dose of HP518 or a period required by local regulation, whichever is longer.

    Part II (Dose Expansion) patients meeting the following criteria will be excluded from the study:

  7. Expression of androgen receptor splice variant 7 (ARV7), a splice variant subtype of the AR.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05252364


Contacts
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Contact: For general questions about this study please contact Hinova Pharma via email HP518@hinovapharma.com

Locations
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Australia, New South Wales
Border Medical Oncology Not yet recruiting
Albury, New South Wales, Australia, 2640
Contact: Craig Underhill    +61260641500    craig.underhill@bordermedonc.com.au   
Chris O'Brien Lifehouse Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Lisa Horvath    +61295157680    lisa.horvath@lh.org.au   
Macquarie University Recruiting
Macquarie Park, New South Wales, Australia, 2113
Contact: Alison Zhang    +61298123500    clinicaltrials@mq.edu.au   
Australia, Victoria
Peter McCallum Cancer Center Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Arun Azad    +61385595000    PCCTU.MoncA@petermac.org   
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3181
Contact: Mark Voskoboynik    +61390763534    m.voskoboynik@alfred.org.au   
Sponsors and Collaborators
Hinova Pharmaceuticals Aus Pty Ltd
Investigators
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Study Director: Zhonghua Zhou Hinova Pharmaceuticals USA, Inc.
More Information
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Responsible Party: Hinova Pharmaceuticals Aus Pty Ltd
ClinicalTrials.gov Identifier: NCT05252364    
Other Study ID Numbers: HP518-CS-001
First Posted: February 23, 2022    Key Record Dates
Last Update Posted: February 27, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
 Neoplasms by Site
Neoplasms
Prostatic Diseases